The New England Journal of MedicineChronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease

The ibrutinib–venetoclax therapy could be a potential game-changer in CLL treatment.

A recent phase 3, multicenter, randomized, controlled, open-label platform trial has shed light on the potential benefits of ibrutinib–venetoclax therapy in patients with untreated chronic lymphocytic leukemia (CLL), compared to the standard fludarabine–cyclophosphamide–rituximab (FCR) regimen.

Study Design

• The study involved patients with untreated CLL.
• The trial compared ibrutinib–venetoclax and ibrutinib monotherapy with FCR.
• A total of 523 patients were randomly assigned to the ibrutinib–venetoclax group or the FCR group.
• In the ibrutinib–venetoclax group, after 2 months of ibrutinib, venetoclax was added for up to 6 years of therapy.
• The duration of ibrutinib–venetoclax therapy was defined by measurable residual disease (MRD) assessed in peripheral blood and bone marrow.

Key Findings

• At a median of 43.7 months, disease progression or death had occurred in 12 patients in the ibrutinib–venetoclax group and 75 patients in the FCR group.
• Death occurred in 9 patients in the ibrutinib–venetoclax group and 25 patients in the FCR group.
• At 3 years, 58.0% of the patients in the ibrutinib–venetoclax group had stopped therapy owing to undetectable MRD.
• After 5 years of ibrutinib–venetoclax therapy, 65.9% of the patients had undetectable MRD in the bone marrow and 92.7% had undetectable MRD in the peripheral blood.

HCN Medical Memo
The use of ibrutinib–venetoclax, guided by MRD levels and including personalized treatment duration beyond the point of undetectable MRD, led to a notable increase in PFS and seemingly improved OS in patients with untreated CLL. The benefits were especially significant in patients who typically have less favorable outcomes with standard treatments, such as those with unmutated IGHV and certain genetic abnormalities.

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